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M J Davicco

Publications and source records attributed to M J Davicco.

At least 37 records · Page 2Linked to original sources
PubMed1998

[Calcitonin and stanniocalcin. Particular aspects of the endocrine regulation of phospho-calcium metabolism in mammals and fish].

The hypocalcemic and hypophosphatemic peptide calcitonin (CT) is secreted by mammalain thyroid parafollicular cells and fish ultimobranchial body. Over a dozen species of CTs have been cloned and/or sequenced. They can be separated into three classes based on structural and biological similarities: teleost/avian, artiodactyl, and human/rat. In mammals, CT exerts its anti-hypercalcemic and hypophosphatemic effects by inhibiting osteoclastic bone resorption and renal tubular phosphate reabsorption, respectively. CT receptors (CTRs) are members of a subfamily of seven-transmembrane domain, G protein-coupled receptors that include those for several other peptide hormones. Basic amino acid substitutions within the CT molecule enhance potency, probably by conferring a helical structure to the peptide. This might explain the enhanced potency of fish CTs for mammalian CTRs. The presence and secretion of salmon CT-like immunoreactive material have been described in both the murine and human central nervous systems, which possess CTRs. These findings are consistent with a role for this peptide acting as a neurotransmitter in mammals. Stanniocalcin (STC) is another hypocalcemic hormone originally identified in fish. In fish STC exerts its anti-hypercalcemic effect by regulating calcium and phosphate transports by the gills, intestine and kidney. Although fish ultimobranchial cells are much less responsive to the secretagogic effects of Ca2+ than mammalian parafollicular cells, the secretion of both CT and STC are positively regulated by extracellular calcium. STC has also been recently identified in humans and rats. It is released by some renal tubular cells and might play a role in the regulation of phosphate metabolism. Nevertheless, the true physiologic roles for CT in fish and STC in mammals, respectively, remain unknown.

Animals↗
PubMed1997

Isolation of cells from ovine fetal long bone and characterization of their osteoblastic activities during in vitro mineralization.

Studies about bone formation and regulation are complex due to a close relationship between bone cells. Primary cell cultures allow to understand osteoblastic function. We isolated cells from the cortical metacarpal bone of 85 or 120 day-old ovine fetuses by an enzymatic method. After first passage and cell amplification, the growth medium (DMEM, ascorbic acid and fetal calf serum 10%) was replaced at confluence by a mineralization medium (MM: DMEM, ascorbic acid, beta-glycerophosphate, insulin). Alkaline phosphatase (ALP) activity in cell-matrix layer increased after 4 days of cultures in MM and maximized at day 6. We also measured osteocalcin, ALP and IGF-I secretion simultaneously during mineralization. PTH, PTHrP and 1.25(OH)2D3 decreased ALP activity in cell-matrix layer after 4 days of treatment in MM without fetal calf serum (FCS). Cells from 120 day-old fetuses were cultivated in MM with 10% FCS during 32 days to induce mineralization. Inorganic phosphorus concentration increased in medium between days 5 and 12, Ca concentration decreased in medium after 12 days of culture. Mineralization started at day 12, in the same time ALP activity appeared in medium. Osteocalcin secretion increased between days 6 and 12, decreased at day 14 and increased from day 16 until day 32. Ovine fetal bone cells produced IGF-I until first days of culture in MM. Such ovine osteoblast phenotype cells having the capacity to differentiate and mineralize in vitro would be a model to study the endocrine regulation of osteoblastic function in large mammals.

Alkaline Phosphatase↗
PubMed1997

Influence of ovariectomy and estradiol treatment on calcium homeostasis during aging in rats.

Study was carried out an Wistar female rats to evaluate the consequences of ovariectomy and 17 beta-estradiol substitutive treatment during aging on bone. Ca metabolism and calciotropic hormones. Three groups of fifteen rats, mature, old and senescent (4-, 10-, and 28 month-old) female were fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi, Within each group, 10 rats were surgically ovariectomized (OVX). From day 1 until day 60 after OVX, they were subcutaneously injected with either 17 beta-estradiol (E: 10 micrograms/kg BW/48 h; n = 5) or with solvent alone (OVX; n = 5). Five other rats were sham operated (SH) and received solvent alone. Animals were put in balance 1 day per week to determine Ca and Pi intestinal apparent absorption and urinary pyridinium cross-links excretion was measured by HPLC. All rats were killed by exsanguination 60 days after OVX. Plasma was collected for measurement of intact parathyroid hormone (PTH), calcitonin (CT), insulin-like growth factor-1 (IGF-1), Ca and Pi. The success of OVX was confirmed at necropsy by observation of marked atrophy of the uterine horns. The right femur was collected, cleaned from adjacent tissue and used for mineral analysis. Despite correct matching for feeding, BW was significantly larger in 6 and 12 month-old OVX rats. OVX and 17 beta-estradiol had no significant effect upon plasma Ca, Pi and CT concentrations. Aging is associated with increased circulating PTH levels (pg/ml) (SH-6 months: 50.8 +/- 12.6; 12 months: 219.1 +/- 34.9; 30 months: 158.7 +/- 23.5; P < 0.05). Urinary and fecal Ca and Pi excretion in senescent animals were higher than in adult or old rats, thus resulting in a drastic fall in both intestinal apparent absorption and retention of Ca and Pi in 30 month-old animals. In each group, urinary pyridinium cross-links excretion and plasma osteocalcin concentration were higher in the OVX animals than in the controls, consistent with increased bone turnover in the estrogen deficient state. Both biochemical turnover markers were reduced in the estrogen-treated groups. In the same way, OVX increased and estrogen decreased the plasma IGF-1 levels. We conclude that 17 beta-estradiol prevents high turnover-induced osteopenia even in 30 month-old rats.

Aging↗
PubMed1997

Influence of sex steroids on development of cultured fetal rat metatarsal bones.

The effects of 17 beta-estradiol (E), dihydrotestosterone (D, a non aromatisable androgen), and progesterone (P) on osteogenesis were studied on fetal rat cartilaginous anlagues cultivated in vitro. The three medial metatarsal rudiments were harvested at day 19 of gestation and grown in 1% BSA MEM medium (MO 643, Sigma) without serum nor antibiotics. After a 18h preincubation period, hormones were added for 8 days. Paired controls were incubated in the same volume of medium. The length, the metacarpal thickness and the size of the mineralized zone were measured every day, using a calibrated eyepiece (magnification X 40). DNA and protein synthesis, cartilage metabolism and mineralization were evaluated by monitoring the incorporation of 3H-Thymidine, 3H-Proline, 35S and 45Ca into anlagues for the last three hours of incubation, respectively. The dose/response effect of each steroid was studied at the concentrations of 10(-4) M, 10(-6) M, 10(-7) M and 10(-9) M. No difference was observed between male and female fetuses. A significant positive effect on total length (% of length measured at harvesting day) was observed with the 10(-7) M dose of E (163% +/- 2 vs 148% +/- 4 in controls) or D (158% +/- 3). Endochondral growth was not modified by P treatment. The effect of the three steroids (given at a dose of 10(-7) M) alone or as combinations (E, D, P, EP, ED, PD, EPD) confirmed the positive effect of E on endochondral growth and, to a lesser extend, of D and the association ED. Nevertheless, D had a better effect than E on endomembranous growth. On the contrary, P did not affect growth neither administrated alone nor in combination with E or D, while a positive effect of P on mineralization was demonstrated. The treatment associating the three steroids slowed down all the parameters concerning growth but strongly stimulated calcification.

Androgens↗
PubMed1996

Influence of ovariectomy on bone metabolism in very old rats.

Twenty-five 30-month-old Lou rats fed a diet (6 g/100 g BW/day) containing 0.9% Ca and 0.8% Pi were divided into five groups. Four groups were surgically ovariectomized. From day 2 until day 29 after ovariectomy, they were S.C. injected either with 17 beta estradiol (E2; 10 micrograms/kg BW/48 hours) or progesterone (P; 140 micrograms/kg BW/48 hours), or 17 beta estradiol + progesterone (E2P) at the same doses, or solvent alone (OVX). The fifth group was sham operated (SH) and injected with solvent. Urine was collected in metabolic cages from day 24 to 29 after ovx, and urinary pyridinoline (PYD) and deoxypyridinoline (DPD) excretion (markers of bone resorption) was measured by HPLC. All animals were killed 30 days after ovariectomy. Serum was then collected for measurement of osteocalcin (OC), alkaline phosphatase (ALP), parathyroid hormone (PTH), and calcitonin (CT). At necropsy, the success of ovariectomy was checked by marked atrophy of the uterine horns. Left and right femur were harvested for densitometric and mineral analysis, respectively. Ovariectomy had no significant effect upon plasma calcium and PTH concentrations. E2 or E2P treatment significantly increased plasma PTH and calcitonin concentrations. Plasma OC concentrations and ALP were not different in any of the groups. In contrast, urinary excretion of PYD and DPD was higher in OVX than in SH rats. Bone mineral density (BMD) of the distal femur was decreased by OVX, but was not different in the E2P and SH groups. A similar pattern was observed for the mineral or Ca content of whole femur. Thus, OVX decreased BMD and bone mineral content (BMC) in very old female rats. Plasma OC concentration and ALP activity failed to demonstrate any significant effect of OVX, whereas PYD and DPD were elevated. These results suggest that bone resorption is increased in OVX rats, even when supplemented with E2 or P alone. However, no significant difference was observed between SH and OVX rats treated with supplementation of both E2 and P. Thus, in very old rats, a combination of E2 and P is much more effective than E2 or P alone to prevent bone loss following ovariectomy.

Aging↗
PubMed1996

Calcitonin mRNA expression and plasma calciotropic hormones in fetal lambs.

The object of this study was to measure basal levels of calciotropic hormones during gestation in the ovine fetus. Thyroid glands and plasma samples were collected from 49 Ile de France x (Limousine x Romanov) fetuses (range, 80 to 145 d). Total thyroidal RNA was extracted for calcitonin (CT) mRNA analysis. Plasma immunoreactive concentrations of CT, parathyroid hormone (PTH), parathyroid hormone-related peptide (PTHrP), and 1,25-dihydroxy-vitamin D [1,25-(OH)2D] were assayed. Plasma Ca and P concentrations were measured by atomic absorption spectrophotometry and colorimetry, respectively. The ratio of thyroidal weight/body weight decreased twice between Days 80 and 145 of gestation. Simultaneously, the CT mRNA rate increased but did not significantly vary after 89 d of gestation. Plasma CT concentration increased between 80 and 89 d and then did not significantly vary until Day 145. We could not detect PTH in ovine fetuses plasma; PTHrP concentration did not vary significantly between Days 80 and 145. The concentration of 1,25-(OH)2D decreased in plasma essentially between Days 110 and 145. In conclusion, between Days 80 and 145 of gestation, CT, PTHrP, and 1,25-(OH)2D concentrations can be easily measured in plasma from ovine fetuses, but plasma PTH was undetectable. In basal conditions, no relationship could be demonstrated between any hormonal concentrations in the fetal plasma and that of Ca or P.

Animals↗
PubMed1996

Water restriction and bone metabolism in camels.

'Krafft disease', occurring in camels living in the very arid areas of North Africa, is characterized by spontaneous fractures of costal and/or appendicular bones. To better understand the mechanisms of this, we studied the influence of water restriction on plasma and urinary markers of bone metabolism in camels. Eight 2-year-old nonpregnant, nonlactating camels were studied at the research station of Laâyoune (Morocco). After a 10 day period of daily watering, five animals were watered only every 10th day over a 50 day period, then again watered daily for a final 10 day period (rehydration). The three control animals were watered daily throughout the whole experimental period (70 days). Each camel was fed a ration of straw, luceme hay and barley, resulting in a daily intake of 25 g calcium and 11 g phosphorus. Water restriction induced a decrease in daily urinary volume and an increase in plasma osmolality. These symptoms of dehydration were not associated with any significant change either in the markers of osteoblastic activity (plasma alkaline phosphatase activity and osteocalcine concentration) or in the markers of bone resorption (urinary excretion of calcium, hydroxyproline pyridinoline and deoxypyridinoline). Thus, in well-fed camels, water restriction did not affect bone metabolism. However, no conclusions were possible regarding the influence of dehydration or calcium and/or phosphorus deficiency in the etiology of 'Kraft disease'.

Alkaline Phosphatase↗
PubMed1996

Metacarpal growth and systemic markers of bone metabolism in the ovine fetus.

Bone metabolism was assessed in 56 Ile de Francex(RomanovxLimousine) fetal lambs killed between Day 80 and Day 145 of gestation. In each fetus, the length, width and weight, as well as the calcium and phosphorus content of the left diaphyseal metacarpal bone were measured. Plasma alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) activities, bone ALP (B-ALP), osteocalcin (OC) and insulin-like growth factor-I (IGF-I) were assayed in these fetuses and in six newborn lambs from birth until one month after birth. Fetal growth is characterized by an increase in bodyweight, bone size and bone mineral content from Day 80 to Day 132 of gestation. These parameters did not significantly vary until birth. Plasma concentrations of IGF-1, OC and B-ALP increased from Day 80 to Day 132. Between Day 132 and birth, plasma IGF-I and B-ALP concentrations did not significantly vary, whereas plasma OC concentration decreased, confirming the usefulness of OC as a marker of osteoblastic activity and bone formation in the ovine species. The increase in plasma IGF-I, B-ALP and OC concentrations observed during the first two weeks of postnatal life indicate an intense skeletal growth in these animals, which was confirmed by the bodyweight growth curve.

Acid Phosphatase↗
PubMed1996

Age-related changes in secretion and metabolic effects of a trial natriuretic factor in rats.

The effects of aging on the secretion of and renal sensitivity to atrial natriuretic factor (ANF) were studied concomitantly in both senescent (25- to 34-month-old) and in adult (7- to 13 month-old) female and male Long-Evans rats. The plasma concentrations of ANF, measured in response to either a mild stimulation induced by a hypertonic volume expansion (i.e., 20 min after the onset of a continuous infusion during 15 min of a 2.5% NaCl solution; n = 18 old and 23 adult rats) or an intense stimulation produced by morphine injection (i.e., 30 min after an intraperitoneal injection of 5 mg morphine/100 g body weight; n = 11 old and 12 adult rats), were significantly lower (approximately -34 and -80%, respectively) in old as compared with adult animals. Acute intravenous injection of exogenous rat ANF (0.10 and 0.40 mu g/100 g body weight) induced similar natriuretic, diuretic, and kaliuretic effects in aged (n = 18) and in adult (n = 23) rats. The present data suggest that the significantly reduced (about -20%) natriuretic and kaliuretic responses of the aged rat, observed 20 min after the onset of hypertonic volume expansion, could be partly due to a primary defect in cardiac production and/or release of ANF rather than to a reduction of renal responsivity to ANF.

Aging↗
PubMed1995

[Relation between the parathyroid glands and arterial pressure: is there a parathyroid hypertensive factor?].

Parathyroid hypertensive factor (PHF) is a newly discovered circulating factor that has been implicated in some forms of hypertension. Such an involvement has been established in several animal models and in hypertensive patients. PHF originates from the parathyroid glands. This explains why hypertensive individuals often have high levels of circulating parathyroid hormone (PTH), which is itself hypotensive. This would reflect the activity of the parathyroid glands, which would produce PHF concomitantly with PTH. The mechanism of action of PHF involves an increase in calcium-channel activity in vascular smooth muscle cells. The opening of these channels would lead to increase calcium entry into these cells, resulting in increased sensitivity to other vasoconstrictors. PHF level explains why a high calcium diet may be effective in lowering blood pressure in patients who respond to calcium-channels blockers: dietary calcium might inhibit the production of PHF (and PTH), whereas calcium-channels blockers would inhibit PHF at its target site.

Biological Factors↗
PubMed1995

Regulation of urinary phosphate excretion in camels.

Urinary inorganic phosphorus (P) excretion was measured in 16 adult female non-pregnant, non-lactating daily watered camels. They were randomly divided into four groups of four animals. Groups 1, 2, and received either an i.v. infusion of phosphate or synthetic human parathyroid hormone (PTH) or PTH-related peptide (PTHrP), respectively. The fourth group was used as a control. Intravenous P loading induced a significant increase in phosphatemia and in P renal clearance. Both PTH and PTHrP increased calcemia and decreased phosphatemia. They had no significant effect on urinary calcium excretion, but they increased P renal clearance and phosphaturia. Thus, the regulation of urinary P excretion in normally watered camels looks similar to that already described in other ruminants.

Animals↗
PubMed1995

EB 1089, a calcitriol analogue, decreases fetal calcium content when injected into pregnant rats.

EB 1089 is a calcitriol analogue with low calcaemic activity, which inhibits parathyroid hormone-related peptide (PTHrP) secretion in rats implanted with the Leydig cell tumour H-500. We have studied its effect on maternal and fetal plasma PTHrP concentrations and on fetal calcium and phosphorus contents in rats. Three groups of six pregnant rats were injected I.P. daily with EB 1089 (0.10, 0.25 and 0.50 microgram kg-1 in groups 1, 2 and 3, respectively, from day 12 to day 20 of gestation). The control group received an equal volume of solvent alone. On day 21 of gestation the animals were anaesthetized with chloral hydrate and blood samples were taken. Fetuses were collected, weighed and ashed for Ca and P measurements. PTHrP concentrations were measured by radioimmunoassay (RIA) in maternal and fetal plasma. Calcium content (mg (g fetal wt)-1; mean +/- S.E.M.) in control fetuses was not different from that measured in fetuses from dams given the lowest dose of EB 1089, but was higher than that in fetuses from rats injected with EB 1089 at 0.25 microgram kg-1 (1.18 +/- 0.20; P < 0.05) or 0.50 microgram kg-1 (1.08 +/- 0.29; P < 0.05). There was no difference in fetal P content between any of the groups of rats. The PTHrP concentration (pg equivalents human PTHrP(1-34) fragment ml-1) in maternal plasma from control rats (1.70 +/- 0.50) was not different from that in maternal plasma of rats given the lowest dose of EB 1089 (1.44 +/- 0.63).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Physical exercise and the skeleton].

The skeleton provides more than only a framework for the body. Bone is a calcified conjunctive tissue sensitive to various mechanical stimuli, mainly to those resulting from gravity and muscular contractions. Numerous animal and human studies demonstrate the importance of weight-bearing physical activity as well as mechanical loading for maintaining skeletal integrity. Lack of weight-bearing activity is dangerous for the skeleton: a decrease in bone mineral density (BMD) has been demonstrated in animals and humans under conditions of weightlessness or immobilization. Other studies have also reported a lower vertebral BMD among young amenorrheic athletes than among athletes with regular cycles and/or non athletes. The main factor responsible for this lower BMD in the amenorrheic athletes is the persistent low level of endogenous estrogen observed among these women. However this does not represent a premature and irreversible loss of bone mass since the resumption of menses following a decrease in training is the primary factor for a significant increase in vertebral BMD in these formerly amenorrheic athletes. A weight-bearing exercise is likely to be more beneficial at weight-bearing than at non weight-bearing sites, and hypogonadism resulting from very intensive training and exercise is more detrimental to trabecular than cortical bone. Bone deficit at non weight-bearing sites may be attenuated by maintenance of body weight. Nevertheless the etiology of "stress fractures" among athletes remains poorly understood, and the exact relationship between soft tissue mass and BMD is not clear. Osteoporosis, the most common bone disorder in France, is a pathological condition associated with increased loss of bone mass, resulting in a greater risk of fracture. Although symptoms of osteoporosis do not generally occur until after menopause, recent evidence suggests that bone loss starts much earlier in life. Therefore osteoporosis might be prevented by increasing peak bone mass and/or by slowering bone loss after menopause. Exercise such as resistance training or weight-bearing activities like running or walking have an osteogenic effect on increasing BMD in young people, and the decrease in BMD is slower in exercised than in non-exercised post-menopausal women. Nevertheless the influence of the length and of the intensity of such physical activities remain to be determined.

Animals↗
PubMed1995

[Physiology of intestinal absorption of phosphorus in animals].

Intestinal absorption of inorganic phosphorus. In most mammalian species inorganic phosphorus (P) is absorbed at the duodenal and jejunal level. However in horses some P is absorbed from the large intestine, whereas in ruminant animals some absorption also takes place in the forestomachs. The structure of the putative phosphate-sodium carrier of the brush border from enterocytes still awaits identification. P absorption is modulated both by endocrine (calcitriol, triiodothyronine) and nutritional factors (minerals of the diet, chemical form of phosphorus). Regulation of salivary P secretion, intestinal absorption of P in ruminants, and its adaptation to diets high or low in P are still poorly understood. Such studies would probably help to decrease the cost of P supplementation in farm animals.

Animals↗
PubMed1994

Renin-aldosterone axis and arginine-vasopressin responses to sodium depletion in camels.

Urinary output, urinary sodium and potassium excretion, plasma electrolyte concentrations and osmolality, plasma renin activity (PRA), and plasma aldosterone and arginine-vasopressin (AVP) concentrations were determined in eight camels in Tadla (Morocco). After administration of furosemide (2 mg.kg-1 body wt) urinary water, sodium and potassium excretions increased, inducing hypovolemia (as reflected by 14.6% increase in hematocrit), hyponatremia (142 +/- 1.0 vs 150 +/- 2.1 mmol.liter-1 in controls; P < 0.05), plasma hypo-osmolality (287.5 +/- 11.5 vs 307 +/- 1.4 mOsm.kg-1 H2O in controls; P < 0.05), and hypokalemia (3.7 +/- 0.2 vs 4.6 +/- 0.1 mmol.liter-1 in controls; P < 0.05). Such body fluid volume and composition changes were associated with parallel increases in PRA and plasma aldosterone concentrations (5.9 +/- 0.6 vs 0.9 +/- 0.2 ng AI.ml-1.hr-1 and 132.4 +/- 35.5 vs 25.1 +/- 6.5 pg.ml-1 in controls, respectively; P < 0.05). They were also associated with a fourfold increase in plasma arginine-vasopressin concentrations (0.8 +/- 0.2 vs 0.2 +/- 0.1 pg.ml-1; P < 0.05). In furosemide-treated animals, plasma aldosterone concentrations correlated positively with PRA (r = 0.85; n = 64; P < 0.01) and negatively with plasma sodium concentrations (r = -0.80; n = 64; P < 0.01), suggesting that in sodium-depleted camels the nexus between the renin-angiotensin system and aldosterone was restored.

Aldosterone↗
PubMed1994

Short communication: parathyroid hormone-related peptide does not stimulate phosphate placental transport.

It has been demonstrated that parathyroid hormone-related peptide (PTHrP) stimulates calcium (Ca) placental transport. Ca and inorganic phosphorous (P) metabolisms are intimately linked. Thus we have studied the influence of PTHrP on P placental transport in ewes. In our experimental paradigm, synthetic human PTHrP (1-86) fragment intravenously injected in six single chronically catheterized fetuses (3 x 1 micrograms/fetus/day, from day 129 to day 140 of gestation) had no significant effect upon P placental transport which was 131 +/- 6 and 129 +/- 9 mg/kg fetal weight/day in treated and control fetuses, respectively.

Animals↗
PubMed1994

Parathyroid hormone (PTH) and PTH-related peptide induce relaxation of smooth muscle cells from guinea pig ileum: interaction with vasoactive intestinal peptide receptors.

PTH-related peptide (PTHrP), which shares 8 of 13 NH2-terminal residues with PTH, causes similar biological effects and interacts with the same receptor as PTH. In the gastrointestinal tract, human PTH and PTHrP-(1-34) relax rat fundic strips. However, the level of their action and the receptor involved in this effect are unknown. The aims of this study were 1) to determine the effects of human PTH-(1-34), human PTHrP-(1-34), -(1-16), and -(7-34) and vasoactive intestinal peptide (VIP) on circular isolated smooth muscle cells from guinea pig ileum; 2) to study the intracellular pathways involved in these effects; and 3) and to characterize the receptors involved by using specific antagonists. Smooth muscle cells were dispersed by enzymatic digestion. Contraction was assessed by measuring the length of 50 cells and expressed as the percent decrease in cell length from the control value. The relaxing effects of PTH, PTHrP and analogs, VIP, or antagonists were expressed as a percentage of the maximal effect observed in their absence. VIP, PTH-(1-34), and PTHrP-(1-34), -(1-16), and -(7-34) had no effect by themselves on these cells. However, when cells were contracted by the sulfated C-terminal octapeptide of cholecystokinin (10 nM), VIP, PTH-(1-34), and PTHrP(1-34) inhibited the sulfated C-terminal octapeptide of cholecystokinin-induced contraction in a concentration-dependent manner, whereas PTHrP-(1-16) and -(7-34) had no effect. The EC50 values of VIP, PTH-(1-34), and PTH-(1-34), and PTHrP-(1-34) were 7 nM, 20 pM, and 20 pM, respectively. The VIP antagonist ([D-P-Cl-Phe6,Leu17]VIP) inhibited VIP-, PTH-(1-34)-, and PTHrP(1-34)-induced relaxation, with IC50 values of 20, 500, and 400 pM, respectively. Likewise, the PTH/PTHrP antagonist [Tyr34-bovine PTH-(7-34)NH2] inhibited PTH-(1-34)-, PTHrP(1-34)-, and VIP-induced relaxation, with IC50 values of 1, 1, and 90 pM, respectively. Preincubation of cells with somatostatin, N-ethylmaleimide, and (R)-p-cyclic adenosine-3',5'-monophosphothioate inhibited the PTH-(1-34), PTHrP(1-34)-, and VIP-induced relaxation. In conclusion, human PTH and PTHrP induce a relaxation of intestinal smooth muscle by a direct myogenic effect. This effect requires the 1-34 amino acid sequence and is mediated by the activation of adenylate cyclase and protein kinase-A. Interactions among PTH, PTHrP, and VIP indicate that they may cross-react with their respective receptors.

Acetylcholine↗